Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in the Auditorium of Kastelli Research Center (Aapistie 1), on April 26th, 2003, at 12 noon.

Tarkastaja(t):

Docent Kaisa Granfors
Docent Marjatta Karvonen

Kuvaus:

Abstract

Chlamydia pneumoniae is a common respiratory pathogen worldwide. It does not only cause acute respiratory infections, but is also associated with chronic inflammatory diseases, such as asthma and coronary heart disease (CHD). Chlamydial heat shock protein 60 (Hsp60) is associated with the development of immunopathological damage following C. trachomatis infections, but the role of Hsp60 in C. pneumoniae infections is unclear. A slightly elevated level of C-reactive protein (CRP), as a marker of systemic inflammation, predicts cardiovascular events, but its role in asthma has not been studied. The aim of this study was to develop an EIA method for the measurement of Hsp60 antibodies and for studying the host immune responses to C. pneumoniae and chlamydial and human Hsp60 proteins, CRP levels and their interactions in asthma and CHD.

Elevated levels of serum IgA antibodies to the Hsp60 protein of C. pneumoniae were associated with asthma and decreased pulmonary function. CRP levels were also higher in the asthma patients than in the controls. The patients with moderate asthma had higher CRP levels than those with mild asthma. The patients with a CRP level over 2 mg/l had higher levels of serum IgA antibodies to C. pneumoniae and chlamydial Hsp60 than the patients with lower CRP levels.

A prospective nested case-control study was carried out, to study the role of Hsp60 antibodies as coronary risk predictors, and their association with C. pneumoniae infection and inflammation. The participants were obtained from the Helsinki Heart Study: 241 myocardial infarctions or coronary deaths occurred during the 8.5-year period among dyslipidemic middle-aged men. An elevated level of human Hsp60 IgA antibodies in baseline serum predicted the occurrence of a coronary event several years later, especially when present simultaneously with a high C. pneumoniae IgA antibody level and an elevated CRP level. Further studies showed that only persistently, not transiently, elevated levels predicted coronary events. The risk associated with elevated antibody levels increased markedly in the presence of an elevated CRP level, and vice versa.

In conclusion, these results suggest that chlamydial Hsp60 is involved in the association between C. pneumoniae infection and asthma, while autoimmunity to human Hsp60 is implicated in the association between C. pneumoniae infection and CHD. Inflammation evidently plays an important role in these associations. It can also be concluded that IgA antibodies, compared to IgG antibodies, against C. pneumoniae and Hsp60 are better markers of chronicity, especially when they are persistently elevated.